US2005271679A1PendingUtilityA1

Recombinant adenylate cyclase toxin of Bordetella induces T cell responses against tumoral antigens

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Assignee: DADAGLIO GILLESPriority: Nov 21, 2003Filed: Nov 22, 2004Published: Dec 8, 2005
Est. expiryNov 21, 2023(expired)· nominal 20-yr term from priority
Inventors:Gilles DadaglioClaude LeclercDaniel LadantBenoit Van Den EyndeSandra MorelCecile Bauche
A61P 31/12A61P 37/00A61P 35/00A61P 37/04F16C 27/066A61K 39/39F16C 19/06A61K 2039/6037C12Y 406/01001F16C 33/7886A61K 47/6415C12N 9/88F16C 25/083A61K 39/099A61K 2039/6068A61K 47/646A61K 38/164A61K 39/0011
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Claims

Abstract

An immunogenic composition comprising a recombinant protein comprising a Bordetella CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen is provided as a cancer treatment. Methods of treatment with this immunogenic composition are also provided. In an embodiment, the therapeutic composition is a treatment for melanoma, and comprises epitopes from the HLA*0201 epitope. These epitopes include Tyr or GnT-V, and are present in the recombinant proteins CyaA-E5-Tyr and CyaA-E5-GnT-V.

Claims

exact text as granted — not AI-modified
1 . An immunogenic composition comprising a recombinant protein, wherein the recombinant protein comprises a  Bordetella  CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen.  
     
     
         2 . The immunogenic composition as claimed in  claim 1 , wherein the  Bordetella  CyaA, or fragment thereof, and the peptide are genetically fused or chemically bound together.  
     
     
         3 . The immunogenic composition as claimed in  claim 1 , wherein the  Bordetella  CyaA is detoxified.  
     
     
         4 . The immunogenic composition as claimed in  claim 1 , wherein the tumor is a melanoma.  
     
     
         5 . The immunogenic composition as claimed in  claim 1 , wherein the tumor antigen is an HLA*0201 epitope.  
     
     
         6 . The immunogenic composition as claimed in  claim 5 , wherein the HLA*0201 epitope is Tyr or GnT-V.  
     
     
         7 . The immunogenic composition as claimed in  claim 5 , wherein the HLA*0201 epitope is region 369-377 of tyrosinase.  
     
     
         8 . The immunogenic composition as claimed in  claim 5 , wherein the HLA*0201 epitope is from an intron of the N-acetylglucosominyl-transferase V gene.  
     
     
         9 . The immunogenic composition as claimed in  claim 5 , wherein the HLA*0201 epitope is YMDGTMSQV (SEQ ID NO: 6).  
     
     
         10 . The immunogenic composition as claimed in  claim 5 , wherein the HLA*0201 epitope is VLPDVFIRC (SEQ ID NO 4).  
     
     
         11 . The immunogenic composition as claimed in  claim 1 , wherein the recombinant protein is CyaA-E5-Tyr br CyaA-E5-GnT-V.  
     
     
         12 . The immunogenic composition as claimed in  claim 1 , wherein the recombinant protein comprises more than one tumor antigen.  
     
     
         13 . The immunogenic composition as claimed in  claim 12 , wherein the tumor antigens are the same or at least one is different from the other(s).  
     
     
         14 . The immunogenic composition as claimed in  claim 1 , wherein the tumor antigen is localized to any permissive site of CyaA.  
     
     
         15 . The immunogenic composition as claimed in  claim 1 , wherein the peptide which corresponds to a tumor antigen includes flanking regions.  
     
     
         16 . The immunogenic composition as claimed in claimed 1, wherein the composition is used as an immunotherapy.  
     
     
         17 . The immunogenic composition as claimed in  claim 1 , wherein the  Bordetella  CyaA is from  B. paratussis, B. parapertussis , or  B. bronchiseptica.    
     
     
         18 . An immunogenic composition comprising a vector wherein the vector expresses a recombinant protein, wherein the recombinant protein comprises a  Bordetella  CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen.  
     
     
         19 . A nucleic acid encoding a fusion protein, wherein the fusion protein comprises  Bordetella  CyaA, or a region thereof, and a peptide that is an antigen comprising the Tyr or GnTV epitope.  
     
     
         20 . A vector expressing a recombinant protein, wherein the recombinant protein comprises  Bordetella  CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen comprising the Tyr or GnTV epitope.  
     
     
         21 . The plasmid deposited at C.N.C.M. under accession number 1-3111.  
     
     
         22 . The plasmid deposited at C.N.C.M. under accession number 1-2679.  
     
     
         23 . A method of treating a patient with cancer comprising (1) administering a immunogenic composition to the patient, wherein the immunogenic composition comprises a recombinant protein, wherein the recombinant protein comprises a  Bordetella  CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen, and (2) inducing a T cell response in the patient.  
     
     
         24 . The method as claimed in  claim 23 , wherein the T cell response is a CTL response.  
     
     
         25 . The method as claimed in  claim 23 , wherein the cancer is a melanoma.  
     
     
         26 . The method as claimed in  claim 23 , wherein the tumor antigen is an HLA*0201 epitope.  
     
     
         27 . The method as claimed in  claim 23 , wherein the HLA*0201 epitope is Tyr or GnT-V.  
     
     
         28 . The method as claimed in  claim 23 , wherein the recombinant protein is CyaA-E5-Tyr or CyaA-E5-GnT-V.  
     
     
         29 . The method as claimed in  claim 23 , wherein the recombinant protein comprises more than one tumor antigen.  
     
     
         30 . The method as claimed in  claim 23 , wherein the tumor antigen is localized to any permissive site of CyaA.  
     
     
         31 . The method as claimed in  claim 23 , wherein the recombinant protein includes flanking regions.  
     
     
         32 . The method of  claim 30 , wherein the tumor antigen is chemically bound to CyaA.  
     
     
         33 . The method of  claim 23 , wherein CyaA is detoxified.  
     
     
         34 . A method of treating a patient with cancer comprising (1) administering an immunogenic composition to the patient, wherein the immunogenic composition comprises a vector expressing a recombinant protein, wherein the recombinant protein comprises a  Bordetella  CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen, and (2) inducing a T cell response in the patient.  
     
     
         35 . The method as claimed in  claim 34 , wherein the T cell response is a CTL response.  
     
     
         36 . The method as claimed in  claim 34 , wherein the cancer is a melanoma.  
     
     
         37 . The method as claimed in  claim 34 , wherein the tumor antigen is an HLA*0201 epitope.  
     
     
         38 . The method as claimed in  claim 34 , wherein the HLA*0201 epitope is Tyr or GnT-V.  
     
     
         39 . The method as claimed in  claim 34 , wherein the recombinant protein is CyaA-E5-Tyr or CyaA-E5-GnT-V.  
     
     
         40 . The method as claimed in  claim 34 , wherein the recombinant protein comprises more than one tumor antigen.  
     
     
         41 . The method as claimed in  claim 34 , wherein the tumor antigen is localized to any permissive site of CyaA.  
     
     
         42 . The method as claimed in  claim 34 , wherein the recombinant protein is modified to include flanking regions.  
     
     
         43 . The method of  claim 41 , wherein the tumor antigen is genetically fused to CyaA.  
     
     
         44 . The method of  claim 34 , wherein CyaA is detoxified.

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